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溃疡性结肠炎的脂质组学研究揭示了与疾病状态相关的黏膜脂质组成的改变。

Lipidomics in Ulcerative Colitis Reveal Alteration in Mucosal Lipid Composition Associated With the Disease State.

机构信息

Natural Products and Medicinal Chemistry Research Group, Department of Pharmacy Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.

Research Group of Gastroenterology and Nutrition, Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.

出版信息

Inflamm Bowel Dis. 2019 Oct 18;25(11):1780-1787. doi: 10.1093/ibd/izz098.

DOI:10.1093/ibd/izz098
PMID:31077307
Abstract

BACKGROUND

The onset of ulcerative colitis (UC) is associated with alterations in lipid metabolism and a disruption of the balance between pro- and anti-inflammatory molecules. Only a few studies describe the mucosal lipid biosignatures during active UC. Moreover, the dynamics of lipid metabolism in the remission state is poorly defined. Therefore, this study aims to characterize mucosal lipid profiles in treatment-naïve UC patients and deep remission UC patients compared with healthy subjects.

METHODS

Treatment-naïve UC patients (n = 21), UC patients in deep remission (n = 12), and healthy volunteers (n = 14) were recruited. The state of deep remission was defined by histological and immunological remission defined by a normalized TNF-α gene expression. Mucosa biopsies were collected by colonoscopy. Lipid analysis was performed by means of ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS-MS). In total, 220 lipids from 11 lipid classes were identified.

RESULTS

The relative concentration of 122 and 36 lipids was altered in UC treatment-naïve patients and UC remission patients, respectively, compared with healthy controls. The highest number of significant variations was in the phosphatidylcholine (PC), ceramide (Cer), and sphingomyelin (SM) composition. Multivariate analysis revealed discrimination among the study groups based on the lipid profile. Furthermore, changes in phosphatidylethanolamine(38:3), Cer(d18:1/24:0), and Cer(d18:1/24:2) were most distinctive between the groups.

CONCLUSION

This study revealed a discriminant mucosal lipid composition pattern between treatment-naïve UC patients, deep remission UC patients, and healthy controls. We report several distinctive lipids, which might be involved in the inflammatory response in UC, and could reflect the disease state.

摘要

背景

溃疡性结肠炎(UC)的发病与脂质代谢改变和促炎与抗炎分子平衡破坏有关。仅有少数研究描述了活动期 UC 中的黏膜脂类生物标志物。此外,缓解期脂质代谢的动态变化还没有明确的定义。因此,本研究旨在比较初治 UC 患者、深度缓解 UC 患者与健康受试者的黏膜脂谱特征。

方法

招募了初治 UC 患者(n = 21)、深度缓解 UC 患者(n = 12)和健康志愿者(n = 14)。深度缓解状态通过组织学和免疫缓解定义,即 TNF-α 基因表达正常化来定义。通过结肠镜检查采集黏膜活检标本。采用超高效液相色谱-串联质谱法(UPLC-MS-MS)进行脂质分析。共鉴定出 11 种脂质类别的 220 种脂质。

结果

与健康对照组相比,初治 UC 患者和 UC 缓解患者的 122 种和 36 种脂质的相对浓度分别发生了改变。变化最显著的是磷脂酰胆碱(PC)、神经酰胺(Cer)和鞘磷脂(SM)组成。多元分析显示,基于脂质谱可以区分研究组。此外,磷脂酰乙醇胺(38:3)、Cer(d18:1/24:0)和 Cer(d18:1/24:2)的变化在各组之间最为明显。

结论

本研究揭示了初治 UC 患者、深度缓解 UC 患者和健康对照组之间黏膜脂类组成模式的差异。我们报告了几种有区别的脂质,它们可能参与了 UC 的炎症反应,并能反映疾病状态。

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